The present invention relates to a method of using a medicament including a local anesthetic in a pertubation procedure for treating dysmenorrhoea and premenstrual syndrome.
The causal relationship between reduced fertility and endometriosis without pelvic adhesions is not clear and neither is the lack of any improved fertility rate after the treatment. Women with endometriosis also suffer from various degrees of dysmenorrhoea and increased occurrence of premenstrual syndrome (PMS). An increased number of leukocytes has been shown in the peritoneal fluid from patients with endometriosis peritoneal implants and has been considered as an ongoing sterile inflammation. Peritoneal fluid macrophages in women with endometriosis may have an increased capacity to resist apoptosis (programmed cell death) and continue to survive which might be crucial for the fertility. Furthermore, phagocytosis of spermatozoa has been found to be increased during incubations for 24 hours in vitro with the peritoneal fluid from patients with endometriosis. It should be noted that endometrium, i.e., the normal mucosa in the uterine cavity, is not the same as endometriosis cells, i.e., endometrium-like cells that grow as a pathological process in the peritoneal cavity or in other locations outside the uterine cavity, that may be cultivated in-vitro as cell lines.
Infertility or sub-fertility is often a dramatic problem for people afflicted therewith. A common treatment of infertile women is IVF (in vitro fertilization) treatment. The basis of the IVF treatment is as follows:
Stimulation of ovulation: Daily hormonal injections, ultrasound examinations and blood samples;
Oocyte retrieval: Ultrasound guided ovarian punctures performed vaginally in local anesthesia;
Preparation of spermatozoa: Swim-up, swim-down, sperm select or other methods to select the optimal population with the best progressive motility;
In vitro fertilization: Incubation of oocytes and the selected population of spermatozoa in a cell incubator. Direct microscopic inspection of cell division and selection of the most vital blastocyte; and
Embryo transfer: 2-3 blastocytes with the best viability is deposited in the uterine cavity for hopeful implantation in the endometrium.
IVF treatment is an expensive method that for some couples initiates complicated psychological side effects. The technical and artificial way of trying to become pregnant has the disadvantages for couples going through the treatment which may adversely affect the relationship. After all the troublesome treatment there is only a pregnancy rate of about 25-30%, leaving those who did not succeed with a damaged relationship and still no child. The cost for IVF treatment is around 20,000-30,000 SEK per menstrual cycle.
In spite of several previous investigations, the reasons for infertility during endometriosis have not been established and neither has the lack of improved fertility rate after treatment. Particularly the relationship is unclear between mild endometriosis and sub-fertility in the absence of pelvic adhesions.
The increased number of leukocytes contained in vivo primed macrophages secreting a macrophage derived growth factor (MDGF) that may explain the proliferation of the endometriosis tissue. Other secretory products from the macrophages, growth factors such as TNF and interferon, exhibit gamete toxicity and may also have an adverse impact on the fertility process.
Also, the cell-free peritoneal fluid is of importance in the reduced fecundity since it has been shown that it significantly reduces the ovum pick-up capacity of the fimbriae of the fallopian tubes. In the peritoneal fluid from patients with endometriosis and unexplained infertility, a reduced progressive velocity of spermatozoa has been found. Even more interesting is the increased phagocytosis of spermatozoa that has been found during incubations for 24 hours in vitro with peritoneal fluid from patients with endometriosis. In that particular study there were, however, several different sperm donors and therefore immunological factors involved cannot be excluded.
The present invention is an alternative method to the IVF treatment for increasing fertility and is also a method for reducing dysmenorrhoea and premenstrual syndrome of women. It has been found by in vitro studies that phagocytosis of spermatozoa is reduced by lidocaine. It is suggested that this effect of lidocaine is due to stabilization of the cell membrane by prohibiting the increase of Na+ permeability and interference with ATP in the cell membrane. The cost for this new fertility treatment will be approximately 10% of the IVF treatment, e.g., 2,500 SEK per menstrual cycle. The method of the present invention has no technical fertilization process that may cause psychological side effects. This treatment can be tried in patients with endometriosis and/or unexplained infertility. It can be carried out while waiting for IVF treatment and does not affect the possibility of successful later IVF treatment.
So far no treatment of infertility with lidocaine is reported in the literature. However, other pharmaceutical effects of lidocaine are known, e.g., as in EP 507 160, which discloses an external preparation for application to the skin containing and lidocaine which comprises a drug-retaining layer placed on a support. The preparation should be used for treatment of herpes zoster neuralgia and postherpetic neuralgia.
More particularly, the present invention relates to a pertubation method of using a local anesthetic that may be used as a treatment against dysmenorrhoea and premenstrual syndrome and for increasing fertility. A pharmaceutical composition may also be used that comprises a pharmaceutically effective dose of the local anesthetic together with a pharmaceutically acceptable excipient.